Methods and systems for determining physiologic characteristics for treatment of the esophagus

ABSTRACT

A method and apparatus for treating abnormal mucosa in the esophagus is disclosed, such that the depth of the treated tissue is controlled. The depth of ablation is controlled by monitoring the tissue impedance and/or the tissue temperature. A desired ablation depth is also achieved by controlling the energy density or power density, and the amount of time required for energy delivery. A method and apparatus is disclosed for measuring an inner diameter of a body lumen, where a balloon is inflated inside the body lumen at a fixed pressure.

CROSS-REFERENCES TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.13/740,418 filed on Jan. 14, 2013, now U.S. Pat. No. 8,876,818, which isa divisional of U.S. patent application Ser. No. 13/189,793, filed onJul. 25, 2011, now U.S. Pat. No. 8,377,055, which is a continuation ofU.S. patent application Ser. No. 12/787,324, filed on May 25, 2010, nowU.S. Pat. No. 8,012,149, which is a continuation of U.S. patentapplication Ser. No. 11/244,385, filed on Oct. 4, 2005, now abandoned,which is a continuation-in-part of U.S. patent application Ser. No.10/754,452, filed on Jan. 9, 2004, now abandoned, which is acontinuation-in-part of U.S. patent application Ser. No. 10/370,645,filed on Feb. 19, 2003, now U.S. Pat. No. 7,530,979, which is adivisional of Ser. No. 09/714,344, filed on Nov. 16, 2000, now U.S. Pat.No. 6,551,310, which claims the benefit under 35 USC 119(e) of U.S.Provisional Application No. 60/165,687, filed on Nov. 16, 1999, each ofwhich are incorporated by reference in their entirety for all purposes.

INCORPORATION BY REFERENCE

All publications and patent applications mentioned in this specificationare herein incorporated by reference to the same extent as if eachindividual publication or patent application was specifically andindividually indicated to be incorporated by reference.

FIELD Field of the Invention

The present invention relates generally to medical methods and systems.More particularly, the invention is directed to methods and systems fortreating and determining physiologic characteristics of body lumens suchas the esophagus.

BACKGROUND

The human body has a number of internal body lumens or cavities locatedwithin, many of which have an inner lining or layer. These inner liningscan be susceptible to disease. In some cases, surgical intervention canbe required to remove the inner lining in order to prevent the spread ofdisease to otherwise healthy tissue located nearby.

Those with persistent problems or inappropriate relaxation of the loweresophageal sphincter can develop a condition known as gastro esophagealreflux disease, manifested by classic symptoms of heartburn andregurgitation of gastric and intestinal contents. The causative agentfor such problems may vary. Patients with severe forms ofgastroesophageal reflux disease, no matter what the cause, can sometimesdevelop secondary damage of the esophagus due to the interaction ofgastric or intestinal contents with esophageal cells not designed toexperience such interaction.

The esophagus is composed of three primary tissue layers; a superficialmucosal layer lined by squamous epithelial cells, a middle submucosallayer and a deeper muscle layer. When gastroesophageal reflux occurs,the superficial squamous epithelial cells are exposed to gastric acid,along with intestinal bile acids and enzymes. This exposure may betolerated, but in some cases can lead to damage and alteration of thesquamous cells, causing them to change into taller, specialized columnarepithelial cells. This metaplastic change of the mucosal epithelium fromsquamous cells to columnar cells is called Barrett's esophagus, namedafter the british surgeon who originally described the condition.

Barrett's esophagus has important clinical consequences, since theBarrett's columnar cells can, in some patients, become dysplastic andthen progress to a certain type of deadly cancer of the esophagus. Thepresence of Barrett's esophagus is the main risk factor for thedevelopment of adenocarcinoma of the esophagus.

Accordingly, attention has been focused on identifying and removing thisabnormal Barrett's columnar epithelium in order to mitigate more severeimplications for the patient. Devices and methods for treating abnormalbody tissue by application of various forms of energy to such tissuehave been described, such as radio frequency ablation. However, withoutprecise control of the depth of penetration of the energy means, thesemethods and devices are deficient. Uncontrolled energy application canpenetrate too deeply into the esophageal wall, beyond the mucosa andsubmucosal layers, into the muscularis externa, potentially causingesophageal perforation, stricture or bleeding. Accordingly, properadministration of the correct amount of treatment energy to the tissuecan be facilitated by knowledge of the size of the esophagus and area tobe treated.

Additionally, medical procedures for treating Barrett's esophagustypically involve deployment of an expandable catheter inside theesophagus. Expandable catheters are preferred because the profile of thecatheter is ideally as small as possible to allow for ease of delivery,while treatment of the esophagus is most efficiently performed when thecatheter is at or slightly larger than the diameter of the esophagealwall. Proper sizing and/or pressurization of the delivery device istherefore desirable to prevent over-distension of the organ, which couldresult in harm to the organ, or under-expansion of the catheter, whichoften results in incomplete treatment. Accordingly, accurate and simplemeasurement of the size of the lumen and control of the pressure of thecatheter on the lumen surface promotes the proper engagement anddelivery of energy to the luminal wall so that a uniform and controlleddepth of treatment can be administered. In addition to calculatingluminal dimensions, the compliance of the lumen can be determined bymeasuring the cross section of the lumen at two or more pressure values.

Therefore, it would be advantageous to have methods and systems foraccurately determining in vivo the size and optionally the compliance ofa body lumen such as the esophagus. In addition, it would be desirableto provide a method and system for treating the body lumen once havingdetermined its size. At least some of these objectives will be met bythe present invention.

DESCRIPTION OF THE BACKGROUND ART

U.S. Pat. No. 5,275,169 describes apparatus and methods for determiningphysiologic characteristics of blood vessels. The device measures thediameter and wall compliance of the blood vessel, and does notadminister treatment. Additionally, the method relies on using only anincompressible fluid to inflate a balloon inside a blood vessel. Otherpatents of interest include U.S. Pat. Nos. 6,010,511; 6,039,701; and6,551,310

SUMMARY OF THE DISCLOSURE

The present invention comprises methods and systems for sizing a bodylumen, such as the esophagus. Methods and systems are also provided fortreating the body lumen once the proper measurements have been made.

Although the following description will focus on embodiments configuredfor treatment of the esophagus, other embodiments may be used to treatany other suitable lumen in the body. In particular, the methods andsystems of the present invention may be used whenever accuratemeasurement of a body lumen or uniform delivery of energy is desired totreat a controlled depth of tissue in a lumen or cavity of the body,especially where such body structures may vary in size. Therefore, thefollowing description is provided for exemplary purposes and should notbe construed to limit the scope of the invention.

In general, in one aspect, the invention features a method for measuringan inner diameter of a body lumen including inserting a balloon in thebody lumen; inflating the balloon inside the body lumen using anexpansion medium; and monitoring a mass of the expansion medium insidethe balloon.

Implementations of the invention can include one or more of thefollowing features. Monitoring the mass of the expansion medium can beperformed using a mass flow sensor. Additionally, the expansion mediumcan be a gas or a liquid. The balloon can be inflated at a fixedpressure, and the fixed pressure can be approximately 4 psig.

In general, in another aspect, the invention features a method fortreating tissue in a body lumen including deploying a selected electrodestructure at the surface of the tissue; delivering energy to theelectrode structure to ablate the tissue to a depth from the surface;and controlling the depth of ablated tissue by monitoring a change intissue impedance.

Controlling the depth of ablated tissue can include monitoring when thetissue impedance reaches a targeted impedance value. In oneimplementation, the targeted impedance value ranges from approximately0.5 ohms to 10 ohms. In another implementation, controlling the depth ofablated tissue can additionally include monitoring when the tissueimpedance changes a specified percentage from an initial tissueimpedance level. In a further implementation, controlling the depth ofablated tissue can include monitoring when the tissue impedance reachesits minimum value. In a particular implementation, the desired depth ofablated tissue is approximately between 0.5 mm and 1 mm.

In general, in another aspect, the invention features a method fortreating tissue of a body lumen, including: deploying an electrodestructure at a surface of the tissue; delivering energy to the electrodestructure to ablate the tissue to a depth from the surface; andcontrolling the depth of tissue ablation of the tissue by monitoring achange in the tissue temperature.

In one embodiment of this aspect of the invention, controlling the depthof tissue ablation includes monitoring when the tissue temperaturereaches a target range. The temperature target range can be betweenapproximately 65° and 95° C., and the energy can be delivered as long asthe measured tissue temperature does not exceed a maximum temperature.In one implementation, the maximum temperature is approximately 95° C.

In general, in another aspect, the invention features a method fortreating abnormal tissue inside a body lumen, including: automaticallydetermining an inner diameter of the body lumen at a location proximalto the abnormal tissue; deploying an electrode structure at a surface ofthe tissue at the proximal location; and delivering energy to theelectrode structure for treating the tissue.

In one embodiment of this aspect of the invention, the inner diameter ofthe body lumen can be determined by automatically inflating anddeflating a balloon inside the body lumen using an expansion medium.This embodiment can further include monitoring a mass of the expansionmedium inside the balloon and controlling a depth of treated tissue. Inone implementation, controlling the depth of treated tissue includescontrolling an amount of power delivered to the tissue over time. Inother implementations, controlling the depth of treated tissue includesnormalizing power delivered to the tissue over time; and/or controllingthe depth of treated tissue by controlling an amount of energy deliveredto the tissue over time; and/or controlling the depth of treated tissueby controlling delivered energy density; and/or controlling the depth oftreated tissue by monitoring and controlling tissue impedance over time;and/or controlling the depth of treated tissue by monitoring andcontrolling tissue temperature over time.

Implementations of the invention can include one or more of thefollowing features. Controlling an amount of power delivered to thetissue by rapidly increasing the power until it reaches a set targetvalue and/or controlling the amount of power delivered by using aproportional integral derivative controller.

In general, in another aspect, the invention features an apparatus fortreating a tissue inside a body lumen including: an electrode structureadapted to be positioned at a surface of the tissue inside the bodylumen, wherein the electrode structure is coupled to an expansionmember; and a generator for producing and delivering energy to theelectrode structure; wherein the generator is adapted to automaticallyinflate the expansion member inside the body lumen and control thepressure inside the expansion member during treatment of the tissue.

Implementations of the invention can include one or more of thefollowing features. The expansion member can be a balloon coupled to acatheter. The apparatus can further include a storage device for storinggenerator settings. In one implementation, the storage device is anEEPROM. The apparatus can further include a pump for automaticallyinflating and deflating the expansion member.

The generator of the apparatus can be adapted to determine an innerdiameter of the body lumen using an inflatable balloon. In oneimplementation, the generator is adapted to control the amount of energydelivered to the tissue over time based on the measured diameter of theesophagus. In another implementation, the generator is adapted tonormalize the density of energy delivered to the tissue based on themeasured diameter of the esophagus. In yet another implementation, thegenerator is adapted to control the amount of power delivered to thetissue over time based on the measured diameter of the esophagus. Inanother implementation, the generator is adapted to control the energydelivered to the electrode structure. In another implementation, thegenerator is adapted to control the power delivered to the electrodestructure. In yet another implementation, the generator is adapted tonormalize the amount of power delivered to the tissue over time based onthe measure diameter of the esophagus. In a further implementation thegenerator is adapted to detect whether a catheter is attached theretoand to identify a characteristic of the attached catheter. In a relatedimplementation, the apparatus can further include a storage deviceadapted to store information about the attached catheter.

The apparatus can further include a footswitch coupled to the generatorand adapted to control the energy delivered to the electrode structureand/or a display for displaying information to a user.

In another implementation, the generator is adapted to be manuallycontrolled by a user such that the user controls the energy delivered tothe electrode structure over time.

The apparatus can further include a proportional integral derivativecontroller adapted to gradually increase power delivered to theelectrode structure until it reaches a set target value.

In general, in another aspect, the invention features an apparatus fortreating a tissue inside a body lumen including: an electrode structureadapted to be positioned at a surface of the tissue inside the bodylumen, wherein the electrode structure is coupled to an expansionmember; and a generator for producing, delivering and controlling energydelivered to the electrode structure; wherein the generator is adaptedto determine an inner diameter of the body lumen.

In one aspect of the invention, a method for treating a body lumen at atreatment location comprises measuring a luminal dimension at thetreatment location of the lumen, selecting an electrode deploymentdevice having an array of electrodes or other electrode structure with apre-selected deployed size which corresponds to the measured dimension,positioning the electrode deployment device at the treatment locationwithin the lumen, deploying the electrode array to the pre-selecteddeployed state to engage a wall of the lumen, and delivering energy tothe electrodes for treatment of the luminal tissue.

In some embodiments, measuring the luminal dimension comprisespositioning a sizing member at the treatment location within the lumen,expanding the sizing member until it engages an inside wall of thelumen, and calculating the luminal dimension at the treatment locationof the esophagus based on the expansion of the sizing member. Often,expanding the sizing member comprises inflating a sizing balloon byintroducing an expansion medium. The expansion medium may be acompressible or non-compressible fluid. In some embodiments, the lumendimensions are calculated by determining the amount of the expansionmedium introduced to the sizing balloon while it is inflated. Forexample, the mass or volume of the expansion medium can be measured byuse of a mass-flow meter or the like. Optionally, a pressure sensor maybe coupled to the sizing balloon, so that the luminal dimension can becalculated from the measured amount of expansion medium introduced tothe balloon at a given pressure. Alternatively, the sizing member maycomprise a basket, plurality of struts, or calipers, or the like. Thelumen may also be measured by ultrasound, optical, or fluoroscopicimaging or by use of measuring strip.

In embodiments where a sizing balloon is employed, the sizing balloonmay comprise any material or configuration. In general, the sizingballoon is cylindrical and has a known length and a diameter that isgreater than the diameter of the target lumen. In this configuration,the sizing balloon is non-distensible, such as a bladder having adiameter in its fully expanded form that is larger than the lumendiameter. Suitable materials for the balloon may comprise a polymer suchas polyimide or polyethylene terephthalate (PET). Alternatively, theballoon may comprise a mixture of polymers and elastomers.

Once the lumen dimensions are determined, an electrode deployment devicematching the measured luminal dimension may be selected from aninventory of devices having different electrode deployment sizes. Insome embodiments, the electrode deployment device is transesophageallydelivered to a treatment area within the esophagus. For example,delivering the device may be facilitated by advancing a catheter throughthe esophagus, wherein the catheter carries the electrode array and anexpansion member. The expansion member may comprise any of the materialsor configurations of the sizing member, such as an inflatablecylindrical balloon comprising a polymer such as polyimide or PET.

In some aspects of the invention, the array of electrodes or otherelectrode structure is arranged on a surface of a dimensionally stablesupport such as a non-distensible, electrode backing. The backing maycomprise a thin, rectangular sheet of polymer materials such aspolyimide, polyester or other flexible thermoplastic or thermosettingpolymer film, polymer covered materials, or other nonconductivematerials. The backing may also comprise an electrically insulatingpolymer, with an electro-conductive material, such as copper, depositedonto a surface. For example, an electrode pattern can be etched into thematerial to create an array of electrodes. The electrode pattern may bealigned in an axial or traverse direction across the backing, formed ina linear or non-linear parallel array or series of bipolar pairs, orother suitable pattern. In many embodiments, delivering energy comprisesapplying radiofrequency (rf) energy to tissue of the body lumen, throughthe electrodes. Depending on the desired treatment effect, theelectrodes may be arranged to control the depth and pattern oftreatment. For treatment of esophageal tissue, the electrode widths areless than 3 mm, typically a width in the range from 0.1 mm to 3 mm,preferably 0.1 mm to 0.3 mm, and adjacent electrodes are spaced apartless than 3 mm, typically in the range from 0.1 mm to 3 mm, preferablyfrom 0.1 mm to 0.3 mm. Alternatively, energy may be delivered by use ofstructures other than those having an array of electrodes. For example,the electrode structure may comprise a continuous electrode arranged ina helical pattern over the balloon.

In another method of the present invention, the measurement of theluminal dimension may be used to determine the amount of energydelivered to the tissue of the lumen. For example, a method for treatingthe tissue of a body lumen at a treatment location comprises measuring aluminal dimension at a location of the lumen, positioning an electrodedeployment device at that location, deploying the expansion member toengage an electrode array to a wall of the lumen; and deliveringsufficient energy to the electrode array for treatment of the luminaltissue based on the measured dimension of the lumen. In general, theamount of power delivered to the electrodes will vary depending on thetype of treatment and the overall surface area of the luminal tissue tobe treated. In some embodiments, the expansion member can variablyexpand to engage the wall of the lumen independent of the size of thelumen. For esophageal treatment, the expansion member may comprise aballoon that can expand to a range of diameters between 12 mm and 50 mm.Typically, the total energy density delivered to the esophageal tissuewill be in the range from 1 J/cm² to 50 J/cm², usually being from 5J/cm² to 15 J/cm². In order to effectively ablate the mucosal lining ofthe esophagus and allow re-growth of a normal mucosal lining withoutcreating damage to underlying tissue structures, it is preferable todeliver the radiofrequency energy over a short time span in order toreduce the effects of thermal conduction of energy to deeper tissuelayers, thereby creating a “searing” effect. It is preferable to deliverthe radiofrequency energy within a time span of less than 5 seconds. Anoptimal time for effective treatment is less than 1 second, andpreferably less than 0.5 second or 0.25 seconds. The lower bound on timemay be limited by the ability of the RF power source to deliver highpowers.

In one aspect of the invention, a method for measuring an internaldimension at a location in a body lumen comprises positioning acylindrical balloon at a location within the lumen, inflating theballoon with an expansion medium to engage an inside wall of the lumen,monitoring the extent of engagement of the balloon, determining theamount of expansion medium in the balloon while inflated at thelocation, and calculating the internal dimension of the esophagus basedon the length of the balloon and the measured amount of expansion mediuminside the balloon. In some embodiments, the balloon istransesophageally delivered to a treatment area within the esophagus byadvancing a catheter carrying the balloon through the esophagus. Often,the balloon is non-distensible and has a diameter that is greater thanthe diameter of the inside wall of the lumen. The balloon may be filledwith an expansion medium that is a compressible fluid, such as air.

Monitoring the extent of engagement comprises determining the expansionof the balloon via a pressure sensor coupled to the balloon, wherein theextent of engagement is determined by the internal pressure exerted fromthe expansion medium as measured by the pressure sensor and by visualverification. The pressure sensor may comprise any device fordetermining the pressure inside a vessel, such as a strain gauge.Alternatively, the extent of engagement may be monitored by determiningthe expansion of the balloon via visual inspection. In some embodiments,the balloon may be expanded to apply pressure to the inside wall of thelumen, thereby causing the lumen to stretch.

In one aspect of the invention, a method for determining wall complianceof an esophagus comprises positioning a balloon at a location within theesophagus, inflating the balloon with a compressible fluid, measuringthe static pressure within the balloon, measuring the total amount offluid within the balloon at least two static pressure values, andcalculating the wall compliance based on the variation in the amount offluid between a first measured pressure and a second measured pressure.For esophageal treatment, the static pressure values to be used aretypically below 10 psig, and preferably at or below 7 psig.

In another aspect, a system for treating tissue of a body lumencomprises a sizing member for measuring the cross section at a locationof the lumen and a catheter having a set of individual treatmentdevices, each device comprising an electrode array adapted to treat atarget location, wherein at least some of the arrays are adapted totreat locations having different sizes determined by the sizing member.In some embodiments, the sizing member comprises an inflatable,noncompliant sizing balloon that is oversized with respect to the insidewall of the lumen. The sizing balloon may be cylindrical with a diameterthat is oversized with respect to the inside wall of the lumen. Thesizing balloon may further be coupled to a pressure sensor fordetermining the internal pressure in the balloon from the introductionof the expansion medium. In addition, the system may further comprise ameasuring means, such as a mass flow meter, for determining the amountof fluid in the sizing balloon.

In some embodiments, each of the individual treatment devices furtherinclude an expansion member comprising an inflatable balloon. Generally,each balloon is cylindrical and ranges in diameter from 12 mm to 50 mmwhen expanded. A balloon within the range is selected based on themeasurement made from the sizing balloon so that when the balloon isexpanded to its fully inflated shape, it properly engages the wall ofthe lumen. Typically, the expansion member is inflated with the samemedium as the sizing balloon. Optionally, the treatment device mayfurther include a pressure sensor as an extra precaution againstover-distension of the organ.

BRIEF DESCRIPTION OF THE DRAWINGS

The novel features of the invention are set forth with particularity inthe claims that follow. A better understanding of the features andadvantages of the present invention will be obtained by reference to thefollowing detailed description that sets forth illustrative embodiments,in which the principles of the invention are utilized, and theaccompanying drawings of which:

FIG. 1 is a schematic view of portions of an upper digestive tract in ahuman.

FIG. 2 is a cross sectional view of a device of the invention insertedin to an esophagus in its relaxed, collapsed state.

FIG. 3 is a cross-sectional view of a device of the invention deployedin an expanded configuration in the esophagus.

FIG. 4 is a schematic view of a sizing device of the invention.

FIG. 5 is a flow chart of a method of the invention for sizing a luminaldimension.

FIG. 6 is a flow chart of a method of the invention for treating luminaltissue

FIG. 7 is a chart of test results performed on calculating the diameterof a vessel by measuring the volume of air used to inflate the balloon.

FIG. 8 is a chart of test results for the air mass required to achievevarious pressure levels in differently sized rigid containers.

FIG. 9 is a schematic view of a treatment device of the invention in acompressed configuration in the esophagus.

FIG. 10 is a schematic view of a treatment device of the invention in anexpanded configuration in the esophagus.

FIG. 11 is a schematic view of another embodiment of a treatment deviceof the invention.

FIG. 12 shows a top view and a bottom view of an electrode pattern ofthe device of FIG. 11.

FIG. 13a-c shows the electrode patterns that may be used with atreatment device of the invention.

FIG. 14a-d shows additional electrode patterns that may be used with atreatment device of the invention.

FIG. 15 shows a flow chart of a method of the invention for determiningthe wall compliance of a lumen.

FIG. 16 illustrates a flow chart of a method for size estimation.

FIG. 17 illustrates an exemplary schematic of a mechanism for performingballoon sizing using a mass flow meter and pressure sensors.

FIG. 18 is an exemplary flowchart of the ablation method.

FIG. 19 illustrates a graphical representation of tissue impedance overtime.

FIG. 20 illustrates a graphical representation of the tissue temperatureover time.

FIG. 21 illustrates an exemplary front panel of the generator.

DETAILED DESCRIPTION

In various embodiments, the present invention provides methods andsystems for measuring, and treating at a controlled and uniform depth,the inner lining of a lumen within a patient. It will be appreciatedthat the present invention is applicable to a variety of differenttissue sites and organs, including but not limited to the esophagus. Atreatment apparatus including a sizing member and a treatment devicecomprising an expandable electrode array is provided. The sizing memberis first positioned at a treatment site within the lumen. Once in place,the sizing member is expanded to engage the wall of the lumen to obtainthe dimensions of the lumen. The sizing member is removed, and at leasta portion of the treatment device is positioned at the tissue site,where the electrode array is expanded to contact the tissue surfaceaccording to the measurements made by the sizing member. Sufficientenergy is then delivered from the electrode array to impart a desiredtherapeutic effect, such as cell necrosis, to a discrete layer oftissue.

Certain disorders can cause the retrograde flow of gastric or intestinalcontents from the stomach 12, into the esophagus 14, as shown by arrowsA and B in FIG. 1. Although the causation of these problems are varied,this retrograde flow may result in secondary disorders, such asBarrett's esophagus, which require treatment independent of and quitedifferent from treatments appropriate for the primary disorder-such asdisorders of the lower esophageal sphincter 16. Barrett's esophagus isan inflammatory disorder in which the stomach acids, bile acids andenzymes regurgitated from the stomach and duodenum enter into the loweresophagus causing damage to the esophageal mucosa. When this type ofretrograde flow occurs frequently enough, damage may occur to esophagealepithelial cells 18. In some cases the damage may lead to the alterationof the squamous cells, causing them to change into taller specializedcolumnar epithelial cells 20. This metaplastic change of the mucosalepithelium from squamous cells to columnar cells is called Barrett'sesophagus. Although some of the columnar cells may be benign, others mayresult in adenocarcinoma.

In one aspect, the present invention provides methods and systems forsizing the esophagus and treating the epithelium of selected sites ofthe esophagus in order to mitigate more severe implications for thepatient. In many therapeutic procedures according to the presentinvention, the desired treatment effect is ablation of the tissue. Theterm “ablation” as used herein means thermal damage to the tissuecausing tissue or cell necrosis. However, some therapeutic proceduresmay have a desired treatment effect that falls short of ablation, e.g.Some level of agitation or damage that is imparted to the tissue toinure a desired change in the cellular makeup of the tissue, rather thannecrosis of the tissue. With the present invention, a variety ofdifferent energy delivery devices can be utilized to create a treatmenteffect in a superficial layer of tissue, while preserving intact thefunction of deeper layers, as described hereafter.

Cell or tissue necrosis can be achieved with the use of energy, such asradiofrequency energy, at appropriate levels to accomplish ablation ofmucosal or submucosal level tissue, while substantially preservingmuscularis tissue. In a particular aspect, such ablation is designed toremove the entire mucosal lining in the treatment region, including theabnormal columnar growths 20 from the portions of the esophagus 14 soaffected, and allow re-growth of a normal mucosal lining.

As illustrated in a cross-sectional view in FIG. 2, the esophagus in itscollapsed, relaxed state does not form a perfect, cylindrical tube.Rather, the walls of the esophagus 14 undulate into a plurality offolds. In this state, the diameter of the esophagus is difficult todetermine, especially by use of visualization techniques such asultrasound or optical imaging. Additionally, uniform treatment of targettissue areas is also difficult because of the irregular surface contoursof the esophageal wall.

In one embodiment of the invention, as illustrated in FIGS. 2, 3 and 4and the flow chart of FIG. 5, a method is disclosed for utilizing asizing device to measure luminal dimensions. The sizing device 40 isfirst delivered to the treatment region in the body lumen, as shown atblock 70. For esophageal sizing as shown in FIG. 2, the esophagus 14will be in a relaxed or collapsed configuration during delivery of thesizing device. The sizing device 40 is in a collapsed configurationduring the delivery of the device to the treatment site in theesophagus. The low profile of the collapsed sizing device 40, as shownin FIG. 2, eases the delivery of the device into the esophagus andminimizes discomfort to the patient. Once the sizing device is orientedin the proper treatment area, an expansion fluid is injected into theballoon, as shown at block 72. The balloon is inflated until it engagesthe inside wall of the lumen, as shown in FIG. 3. During the infusion ofthe expansion medium, the extent of engagement of the balloon ismonitored, as well as the amount of expansion medium being injected intothe balloon, as shown by block 74. Once the balloon properly engages thelumen wall (shown at block 76), the final mass or volume of expansionmedium is recorded so that the internal dimension of the esophagus maybe calculated, shown at blocks 78, 82. The sizing balloon is thendeflated so that it can be readily removed from the treatment site,shown at block 80.

Referring to FIGS. 2, 3, 4, a device of the present invention comprisesa sizing device 40 for determining the dimensions of a treatment lumen.The device 40 has an expansion member 42 that is inserted into a lumenin a collapsed configuration and expanded upon proper placement at apre-selected treatment area. In a preferred configuration, the expansionmember 42 is a cylindrical balloon with a native diameter that isoversized so that it will be larger in its fully expanded configurationthan the expected diameter of the treatment lumen. The balloon 42comprises a thin, flexible, bladder made of a polymer material, forexample polyimide, polyurethane, pet, or the like. The balloon isattached to a catheter sleeve 44, wherein the balloon is disposed on thedistal end 46 of the catheter sleeve for infusing an expansion mediuminto the balloon from an infusion source is. Infusion source isconnected to an access port 50 of a y-connector located at the proximalend 48 of the catheter sleeve 44.

Ideally, the expansion medium comprises a compressible fluid, such asair. The expansion medium may alternatively comprise an incompressiblefluid, such as water, saline solution, or the like. It would beunderstood by one of skill in the art that sizing a body lumen bymonitoring the mass of an expansion medium advantageously can beaccomplished using either compressible or incompressible fluids.Infusion of the expansion medium into the sizing balloon may beaccomplished by a positive displacement device such as a fluid-infusionpump or calibrated syringe driven by stepper motor or by hand.Alternatively, for a compressible expansion medium, pressurized air orgas may also be used. In many embodiments, the sizing device alsocomprises a means for determining the amount of expansion fluidtransferred to the balloon, such as a calibrated syringe. A mass orvolume flow meter may be coupled to the fluid delivery source forsimultaneously measuring the amount of fluid in the balloon as it isinflated.

As the expansion medium is injected into balloon 42, the balloon expandsradially from its axis to engage the wall of the lumen. For esophagealtreatment, the walls of the esophagus 14 unfold to form a morecylindrical shape as balloon 42 expands, as illustrated in FIG. 3. Inthis configuration, internal diameter dl of the esophagus 14 is readilycalculated based on the length 1 of the balloon and the measured amountof expansion medium inside the balloon. Balloon 42 is oversized so thatthe diameter D2 of the balloon when unrestrained and fully inflated islarger than the diameter of the balloon when constrained in the lumen.Although an inflatable balloon is generally preferred, the sizing membermay comprise a basket, plurality of struts, calipers, or the likeinstrument for determining the internal diameter of a tubular member.

Tests were performed to calculate the inside diameter of a member byusing volume flow measurements. Various types and sizes of tubes weretested by measuring the mass of air used to inflate an oversized bladderinside the tube. As shown in FIG. 7, the diameter of the tube can berepeatably estimated by measuring the volume of air delivered into theballoon.

In some embodiments of the invention, a pressure sensor may be coupledto the sizing device, wherein the extent of engagement is determined bythe internal pressure exerted from the expansion medium as measured bythe pressure sensor or visual verification.

The pressure sensor may comprise any device for determining the pressureinside a vessel, such as a strain gauge. In FIG. 4, the pressure sensorPS is located at access port 52 at the proximal end of the cathetersleeve 44. Alternatively, the pressure sensor can be located inside theballoon 42. As the balloon expands to engage the wall of the lumen, thepressure in the balloon increases as a result of the constraint on theballoon from the lumen wall.

Because the balloon is oversized and not at its fully extended diameterwhen contacting the lumen wall, the pressure in the balloon is equal tothe contact force per unit area against the lumen wall. Therefore, thepressure inside the balloon is directly proportional to the contactforce on the lumen wall. Furthermore, the balloon may be expanded toapply pressure to the inside wall of the lumen, thereby causing thelumen to stretch. Generally, the sizing balloon will be inflated to apressure corresponding to the desired pressure for treatment of thelumen. For esophageal treatment, it is desirable to expand the treatmentdevice sufficiently to occlude the vasculature of the submucosa,including the arterial, capillary, or venular vessels. The pressure tobe exerted to do so should therefore be greater than the pressureexerted by such vessels, typically from 1 psig to 10 psig, preferablyfrom 4 psig to 7 psig and more preferably from 2 psig to 3 psig.

In some embodiments, the measurement of the pressure inside the balloonmay be used to monitor the extent of engagement of the balloon with thelumen wall. Alternatively, the extent of engagement may be monitored bydetermining the expansion of the balloon via visual inspection with useof an endoscope, or by ultrasound, optical, or fluoroscopic imaging (notshown).

Tests were performed on different sized rigid tubes to calculate theamount of mass required to inflate an oversized balloon in a constrainedtube at various pressures. As shown in FIG. 8, the test results showedpredictable linear relationships between the measured inflated air massand the tube diameter for each pressure range tested.

As shown in the flow chart of FIG. 6, a method and system of the presentinvention is disclosed for treating a luminal tissue. Similar to themethod described in FIG. 5, a sizing device is used to calculate theinternal diameter of the lumen, as shown at block 84. The measurementobtained from the sizing device is then used to select a treatmentdevice from an array of different sized catheters, shown at block 86.The device is then inserted into the body lumen and delivered to thetreatment site, as shown at block 88. An expansion fluid is theninjected into the device by an infusion source like that of the sizingdevice as shown in block 90. Because the catheter is selected to have anouter diameter when fully expanded that appropriately distends theluminal wall, it is not necessary to monitor the expansion of thecatheter. However, the pressure and fluid volume of expansion mediumdelivered to the treatment device can be monitored as a precautionarymeasure, as shown in blocks 92 and 94. With the catheter properlyengaged to the luminal wall at the treatment site, energy, such as RFenergy, is delivered to the catheter for treatment of the luminaltissue, as shown at block 96. Once treatment has been administered, thecatheter is deflated for removal from the lumen as shown in block 98.

As illustrated in FIGS. 9 and 10, a treatment device 10 constructed inaccordance with the principles of the present invention, includes anelongated catheter sleeve 22 that is configured to be inserted into thebody in any of various ways selected by the medical provider. Fortreatment of the esophagus, the treatment device may be placed, (i)endoscopically, e.g. Through esophagus 14, (ii) surgically or (iii) byother means.

When an endoscope (not shown) is used, catheter sleeve 22 can beinserted in the lumen of the endoscope, or catheter sleeve 22 can bepositioned on the outside of the endoscope. Alternately, an endoscopemay be used to visualize the pathway that catheter 22 should followduring placement. As well, catheter sleeve 22 can be inserted intoesophagus 1014 after removal of the endoscope.

An electrode support 24 is provided and can be positioned at a distalend 26 of catheter sleeve 22 to provide appropriate energy for ablationas desired. Electrode support 24 has a plurality of electrode areasegments 32 attached to the surface of the support. The electrodes 32can be configured in an array 30 of various patterns to facilitate aspecific treatment by controlling the electrode size and spacing(electrode density). In various embodiments, electrode support 24 iscoupled to an energy source configured for powering the array 30 atlevels appropriate to provide the selectable ablation of tissue to apredetermined depth of tissue. The energy may be deliveredcircumferentially about the axis of the treatment device in a singlestep, i.e., all at one time. Alternatively, the energy may be deliveredto different circumferential and/or axial sections of the esophagealwall sequentially.

In many embodiments, the support 24 may comprise a flexible,non-distensible backing. For example, the support 24 may comprise of athin, rectangular sheet of polymer materials such as polyimide,polyester or other flexible thermoplastic or thermosetting polymer film.The support 24 may also comprise polymer covered materials, or othernonconductive materials. Additionally, the backing may include anelectrically insulating polymer, with an electro-conductive material,such as copper, deposited onto a surface so that an electrode patterncan be etched into the material to create an array of electrodes.

Electrode support 24 can be operated at a controlled distance from, orin direct contact with the wall of the tissue site. This can be achievedby coupling electrode support 24 to an expandable member 28, which has acylindrical configuration with a known, fixed length, and a diametersized to match at its expanded state the calculated diameter of theexpanded (not collapsed) lumen. Suitable expandable members include butare not limited to a balloon, non-compliant balloon, balloon with atapered geometry, cage, frame, basket, plurality of struts, expandablemember with a furled and an unfurled state, one or more springs, foam,bladder, backing material that expands to an expanded configuration whenunrestrained, and the like. For esophageal treatment, it is desirable toexpand the expandable member to distend the lumen sufficiently toocclude the vasculature of the submucosa, including the arterial,capillary, or venular vessels. The pressure to be exerted to do soshould therefore be greater than the pressure exerted by such vessels,typically from 1 psig to 10 psig, preferably from 4 psig to 7 psig andmore preferably from 2 psig to 3 psig. Generally, the expandable memberfor the treatment device will be selected to match the diameter measuredby the sizing device at the desired pressure. Under this configuration,full expansion of the expandable member will result in a pressure thatproperly distends the luminal wall. In some embodiments, it may bedesirable to employ a pressure sensor or mass flow meter (not shown) asa precautionary measure so that over-distension of the lumen does notoccur.

As shown in FIGS. 9 and 10, the electrode support 24 is wrapped aroundthe circumference of expandable member 28. In one system of the presentinvention, a plurality of expandable members can be provided wherein thediameter of the expandable member varies from 12 mm to 50 mm whenexpanded. Accordingly, the system may include a plurality of electrodesupports, each sized differently corresponding to the different sizedexpandable members. Alternatively, the electrode support 24 may beoversized to be at least large enough to cover the circumference of thelargest expandable member. In such a configuration, the electrodesupport overlaps itself as it is wrapped around the circumference of theexpandable member, similar to the electrode support of device 100illustrated in FIG. 11, discussed infra.

In another embodiment, expandable member 28 is utilized to deliver theablation energy itself. An important feature of this embodiment includesthe means by which the energy is transferred from distal end 26 toexpandable member 28. By way of illustration, one type of energydistribution that can be utilized is disclosed in U.S. Pat. No.5,713,942, incorporated herein by reference, in which an expandableballoon is connected to a power source, which provides radio frequencypower having the desired characteristics to selectively heat the targettissue to a desired temperature. Expandable member 28 may be constructedfrom electrically insulating polymer, with an electro-conductivematerial, such as copper, deposited onto a surface so that an electrodepattern can be etched into the material to create an array ofelectrodes.

Electrode support 24 can deliver a variety of different types of energyincluding but not limited to, radio frequency, microwave, ultrasonic,resistive heating, chemical, a heatable fluid, optical including withoutlimitation, ultraviolet, visible, infrared, collimated ornon-collimated, coherent or incoherent, or other light energy, and thelike. It will be appreciated that the energy, including but not limitedto optical, can be used in combination with one or more sensitizingagents.

The depth of treatment obtained with treatment device 10 can becontrolled by the selection of appropriate treatment parameters by theuser as described in the examples set forth herein. One importantparameter in controlling the depth of treatment is the electrode densityof the array 30. As the spacing between electrodes decreases, the depthof treatment of the affected tissue also decreases. Very close spacingof the electrodes assures that the current and resulting ohmic heatingin the tissue is limited to a very shallow depth so that injury andheating of the submucosal layer are minimized. For treatment ofesophageal tissue using RF energy, it may be desirable to have a widthof each RF electrode to be no more than, (i) 3 mm, (ii) 2 mm, (iii) 1 mm(iv) 0.5 mm or (v) 0.3 mm (vi) 0.1 mm and the like. Accordingly, it maybe desirable to have a spacing between adjacent RF electrodes to be nomore than, (i) 3 mm, (ii) 2 mm, (iii) 1 mm (iv) 0.5 mm or (v) 0.3 mm(vi) 0.1 mm and the like. The plurality of electrodes can be arranged insegments, with at least a portion of the segments being multiplexed. AnRF electrode between adjacent segments can be shared by each of adjacentsegments when multiplexed.

The electrode patterns of the present invention may be varied dependingon the length of the site to be treated, the depth of the mucosa andsubmucosa, in the case of the esophagus, at the site of treatment andother factors. The electrode pattern 30 may be aligned in axial ortraverse direction across the electrode support 24, or formed in alinear or non-linear parallel matrix or series of bipolar pairs ormonopolar electrodes. One or more different patterns may be coupled tovarious locations of expandable member 28. For example, an electrodearray, as illustrated in FIGS. 13(a) through 13(c), may comprise apattern of bipolar axial interlaced finger electrodes 68, six bipolarrings 62 with 2 mm separation, or monopolar rectangles 65 with 1 mmseparation. Other suitable RF electrode patterns which may be usedinclude, without limitation, those patterns shown in FIGS. 14(a) through14(d) as 54, 56, 58 and 60, respectively. Pattern 54 is a pattern ofbipolar axial interlaced finger electrodes with 0.3 mm separation.Pattern 56 includes monopolar bands with 0.3 mm separation. Pattern 60includes bipolar rings with 0.3 mm separation. Pattern 58 is electrodesin a pattern of undulating electrodes with 0.2548 mm separation.

A probe sensor may also be used with the system of the present inventionto monitor and determine the depth of ablation. In one embodiment, oneor more sensors (not shown), including but not limited to thermal andthe like, can be included and associated with each electrode segment 32in order to monitor the temperature from each segment and then be usedfor control. The control can be by way of an open or closed loopfeedback system. In another embodiment, the electroconductive member canbe configured to permit transmission of microwave energy to the tissuesite. Treatment apparatus 10 can also include steerable and directionalcontrol devices, a probe sensor for accurately sensing depth ofablation, and the like.

Referring to FIG. 11, one embodiment of the invention comprises anelectrode deployment device 100 having an electrode support 110 furledaround the outside of an inflatable balloon 116 that is mounted on acatheter sleeve 118. Support 110 has an electrode array 112 etched onits surface, and is aligned between edges 120 that intersect the taperregion located at the distal and proximal ends of balloon 116. Support110 may be attached at a first end 122 to balloon 116 with an adhesive.The second end 124 of the support is furled around the balloon,overlapping the first end 122. Alternatively, support 110 may beretained in a compressed furled state around balloon 116 by an elasticband 123. In such a configuration, the adhesive need not be applied toattach first end 122 to balloon 116, thus allowing for rapid placementor exchange of the appropriately sized balloon 116 to match measurementsmade from the sizing device 10 illustrated in FIG. 4.

FIG. 12 shows a bottom view 150 and a top view 152 of the electrodearray 112 of support 110. In this embodiment, the array 112 has 20parallel bars, 0.25 mm wide, separated by gaps of 0.3 mm. The bars onthe circuit form twenty complete continuous rings around thecircumference of balloon 116. Electrode array 112 can be etched from alaminate consisting of copper on both sides of a polyimide substrate.One end of each copper bar has a small plated through hole 128, whichallows signals to be passed to these bars from 1 of 2 copper junctionblocks 156 and 158, respectively, on the back of the laminate. Onejunction block 156 is connected to all of the even numbered bars, whilethe other junction block 158 is connected to all of the odd numberedbars.

As shown in FIGS. 11 and 12, each junction block 156 and 158 is thenwired to a bundle of awg wires 134. The wiring is external to balloon116, with the distal circuit wires affixed beneath the proximal circuit.Upon meeting the catheter sleeve of the device, these bundles 134 can besoldered to three litz wire bundles 136. One bundle 136 serves as acommon conductor for both circuits while the other two bundles 136 arewired individually to each of the two circuits. The litz wires areencompassed with heat shrink tubing along the entire length of thecatheter sleeve 118 of the device. Upon emerging from the proximal endof the catheter sleeve, each of these bundles 136 is individuallyinsulated with heat shrink tubing before terminating to a mini connectorplug 138. Under this configuration, power can be delivered to either orboth of the two bundles so that treatment can be administered to aspecific area along the array.

The y connector 142 at the proximal end of the catheter sleeve includesaccess ports for both the thru lumen 144 and the inflation lumen 146.The thru lumen spans the entire length of the balloon catheter and exitsthrough lumen tip 148 at the distal end of balloon 116. The inflationlumen 146 is coupled to balloon 116 so that the balloon can be inflatedby delivery of a liquid, gaseous solution such as air, or the like.

In some embodiments, for delivery of apparatus 100, support 110 istightly furled about deflated balloon 116 and placed within a sheath(not shown). During deployment, this sheath is retracted along the shaftto expose support 110. In alternative embodiments, an elastic member 123may be coupled to the support 110 to keep the support furled aroundballoon 116 during deployment of apparatus 100.

In order to ensure good contact between the esophageal wall andelectrode array 112, slight suction may be applied to the through lumentube to reduce the air pressure in the esophagus 14 distal to balloon116. The application of this slight suction can be simultaneouslyapplied to the portion of the esophagus 14 proximal to balloon 116. Thissuction causes the portion of the esophageal wall distended by balloon116 to be pulled against electrode arrays 112 located on balloon 116.

Apparatus 100, illustrated in FIG. 11, is designed for use with the RFenergy methods as set forth herein. Electrode array 112 can be activatedwith approximately 300 watts of radio frequency power for the length oftime necessary to deliver an energy density from 1 J/cm² to 50 J/cm². Todetermine the appropriate level of energy, the diameter of the lumen isevaluated so that the total treatment area can be calculated. A typicaltreatment area of 10 cm² will require total energy ranging from 10 j to500 j. In one embodiment, controlling the depth of treated tissue caninclude normalizing the amount of power delivered to the tissue overtime. In this context, normalizing power delivered means equivalentpower densities (i.e., power unit area of electrode surface area{W/cm²}) are delivered to esophagi of differing diameters. In anotherembodiment, controlling the depth of treated tissue comprisescontrolling the amount of delivered energy density. Such can beaccomplished by normalizing the amount of energy delivered to tissueover time so that equivalent energy densities (i.e., energy per unitarea of electrode surface area {J/cm²}) are delivered to esophagi ofdiffering diameters.

In order to effectively ablate the mucosal lining of the esophagus andallow re-growth of a normal mucosal lining without creating damage tounderlying tissue structures, it is preferable to deliver theradiofrequency energy over a short time span in order to reduce theeffects of thermal conduction of energy to deeper tissue layers, therebycreating a “searing” effect. It is preferable to deliver theradiofrequency energy within a time span of less than 5 seconds. Anoptimal time for effective treatment is less than 1 second andpreferably less than 0.5 second or 0.25 second. The lower bound on timemay be limited by the ability of the RF power source to deliver highpowers, or alternatively by the required depth of treatment. Since theelectrode area and consequently the tissue treatment area can be as muchas several square centimeters, RF powers of several hundred watts wouldbe required in order to deliver the desired energy density in shortperiods of time. This may pose a practical limitation on the lower limitof time. However, an RF power source configured to deliver a very short,high power, pulse of energy could be utilized. Using techniques similarto those used for flash lamp sources, or other types of capacitordischarge sources, a very high power, short pulse of RF energy can becreated. This would allow treatment times of a few msec, or less. Whilethis type of approach is feasible, in practice a more conventional RFsource with a power capability of several hundred watts may bepreferred.

The energy source may be manually controlled by the user and is adaptedto allow the user to select the appropriate treatment time and powersetting to obtain a controlled depth of ablation. The energy source canbe coupled to a controller (not shown), which may be a digital or analogcontroller for use with the energy source, including but not limited toan RF source, or a computer with software. When the computer controlleris used it can include a CPU coupled through a system bus. The systemmay include a keyboard, a disk drive, or other non volatile memorysystem, a display and other peripherals known in the art. A programmemory and a data memory will also be coupled to the bus.

In some embodiments of the present invention, systems and methods aredisclosed for treating luminal tissue with a single treatment devicethat variably expands to accommodate a number of different sized lumens.Preferably, the treatment device comprises a furled electrode supportthat variably engages the luminal wall while keeping the electrodedensity constant. Such approaches are described in detail in co-pendingapplication Ser. No. 10/754,444, the full disclosure of which isincorporated herein by reference. For example, for the treatment device100 shown in FIG. 11, which employs a variable exposed-length electrodearray 112, balloon 116 may be oversized with respect to the size of thelumen so that it can be expanded to accommodate differing luminaldimensions from patient to patient. Measurements from sizing device 10can be used to scale as needed the desired power and energy settings todeliver the same power and energy per unit area. These changes can bemade either automatically or from user input to the RF power source. Ifdifferent treatment depths are desired, the geometry of electrode array112 can be modified to create either a deeper or more superficialtreatment region. Making the electrodes of array 112 more narrow andspacing the electrodes closer together reduces the treatment depth.Making the electrodes of array 112 wider, and spacing the electrodesfurther apart, increases the depth of the treatment region. Non-uniformwidths and spacings may be exploited to achieve various treatmenteffects.

Referring to FIG. 15, the sizing device may be used as a method fordetermining the lumen diameter and wall compliance of one or moresections of the esophagus. A sizing device having an inflatable balloonlike that of device 40 illustrated in FIG. 5 is inserted into theesophagus in a compressed configuration and positioned at a locationwithin the esophagus, as shown at block 200. The balloon is theninflated with a compressible fluid so that the balloon engages theinside wall of the esophagus and distends the wall of the esophagus,shown at block 202. While the expansion medium is delivered to theballoon, the static pressure inside the balloon is monitored with apressure sensor and the amount of expansion medium delivered to theballoon is measured, shown at block 204. The pressure may be measured atthe infusion source with strain gauge or the like. Alternatively, thepressure can be measured at a location inside the balloon with amicrominiature pressure transducer or the like. The amount of expansionmedium delivered to the balloon may be measured by a mass-flow meter orthe like. Once a first target pressure (P1) inside the balloon isachieved, a corresponding first mass or volume measurement (M1) isrecorded, as shown at blocks 206 and 208. The values of P1 and M1 areused to calculate the lumen diameter at pressure P1, using therelationship previously determined and shown in FIG. 8, block 200 ofFIG. 15, or other equivalent means. Additional expansion medium is thendelivered to the balloon, and the static pressure and the total amountof expansion medium within the balloon are monitored, shown at blocks210 and 212. This continues until a second target pressure (p2) insidethe balloon is achieved, and a corresponding second mass or volumemeasurement (m2) is recorded, as shown at blocks 214 and 216.Calculation of the lumen diameter at pressure P2 is performed aspreviously described and shown in block 220. The sizing balloon is thendeflated and then removed from the esophagus as shown in block 218.Target pressure values P1 and P2 are generally set at values that causethe esophagus to distend, but not over-distend. Typical target pressurevalues range from 1 psig to 7 psig, preferably from 4 psig to 7 psig andmore preferably from 2 psig to 3 psig. Wall compliance of the esophagusis then determined based on the variation in the calculated lumendiameter between a first measured pressure P1 and a second measuredpressure P2, as shown in block 222.

FIG. 21 is an exemplary front panel of a generator system according toone embodiment of the invention. In one embodiment, the generator 230produces, delivers and controls power, such as RF power. Other functionsof the generator 230 include controlling inflation and deflation of thesizing balloon, estimating the diameter of the sizing balloon, selectivedelivery of RF power and energy to a treatment catheter and specificelectrodes within the treatment catheter, and displaying variousinformation to a user. To deliver various information regarding useparameters and status of the system, the front panel of the generator230 incorporates various controls, displays and indicators.

The generator 230 connects to the catheter 22 through the RF andcommunication (Python) cable 234. When the generator 230 is connected toa catheter, the generator is capable of detecting whether it is a sizingcatheter, used for determining the size of the esophagus, or a treatmentcatheter, used for ablation. The generator 230 reads from a storagedevice the type of catheter that is connected thereto. The storagedevice stores various catheter specific information and sizing specificparameters. For example, the storage device contains various generatorsettings for each diameter ranges. Further, the generator 230 may causeadditional information to be stored, recommended catheter size afterballoon auto-sizing is performed or the number of ablations performed.It should be noted that the storage device may be any suitable storagedevice, such as an EEPROM.

When the generator 230 detects a sizing catheter, the generator 230performs an estimation of the balloon diameter. In order to reduceuncertainty in the diameter measurement, a calibration of the balloonmay be performed, using control 264. During calibration, the volume ofgas needed to fully expand the unconstrained balloon is determined, andwill be used to determine a calibration constant. Using a mass flowsensor, the generator 230 measures the total gas or fluid mass requiredto inflate the sizing balloon to a specific pre-determined pressure.This predetermined pressure is a clinically safe pressure to perform thesizing of the esophagus and is chosen to ensure that inflation of theballoon within the esophagus would not rupture the esophagus whilestretching and smoothing its lining. In order to initially evacuate allthe gas in the balloon, the balloon is inflated to a pressure ofapproximately 4 psig, then deflated to a negative pressure ofapproximately up to −4 psig, and then inflated again to about 4 psig.Fluid or gas is delivered to the balloon using a pneumatic connectioncable 236. Upon depression of the automatic inflation button 240, thegenerator will deliver air to the balloon according the sizing catheterinflation pressure. It should be noted that the balloons on either thetreatment catheter or the sizing catheter may be inflated or deflatedusing the control buttons 240 and 241. While the balloon is inflated,the balloon pressure may be continuously displayed on display 251.

Before inserting the sizing balloon in the esophagus to measure itseffective diameter at a given inflation pressure (nominal 4 psig) eachballoon is first calibrated in air. The calibration process involvesattaching the sizing balloon to the pneumatic connection cable 236 andgenerator 230 and first pulling a vacuum (typical pressure values rangefrom 0 to −6 psig, nominal −4 psig) to fully collapse the balloon. Nexta mass flow sensor of the generator 230 is used to accurately measurethe amount of air necessary to fill the balloon (nominal 33.7 mmdiameter) to 4 psig, thereby solving the relationship between volume andpressure for that balloon size and shape. This calibration informationsubsequently enables diameter measurements of the esophagus by measuringthe amount of air necessary to inflate the balloon to a specificdiameter.

Once balloon calibration is complete, the sizing balloon is introducedin the esophagus and repositioned at various locations within theesophagus. For each one of these locations, the generator 230 estimatesthe diameter of the balloon and effectively the esophagus diameter atthe set pressure and then automatically recommends an ablation ballooncatheter diameter to be subsequently used. The generator 230 will thendisplay the recommended balloon diameter on display 250. Afterauto-sizing is performed, the system will automatically deflate thesizing catheter balloon to a negative pressure of approximately −2 psigor less.

FIG. 16 is an exemplary flow chart of the method for measuring the sizeof the esophagus and finding the most proximal Barrett's esophaguslocation or other areas to be ablated. At step 160, a sizing catheter isconnected to the generator. The specific characteristics of the sizingcatheter are recognized by the generator from the storage device, suchas: whether and when the catheter has been used before, and whether theballoon has already met a maximum number of allowed inflations. Thesystem is ready for calibrating the balloon at step 161 if the catheterand the balloon are optimal for use. For better accuracy, the balloon isunconstrained in air during calibration. At step 163, the balloon goesthrough the inflate-deflate-inflate cycle such that the mass flow sensordetermines the volume in the balloon at a pre-set pressure. Whencalibration is complete, the balloon automatically deflates and isintroduced into the esophagus for sizing, as shown at step 164. Theballoon is inflated again inside the esophagus at various locations toestimate the inner diameter of the esophagus. At step 165, a first sizeis displayed and a stand by state is indicated on the front panel of thegenerator. The sizing routine is repeated at various locations in theesophagus to find the location of the abnormal cells and determine therecommended catheter size, as shown in steps 166, 167 and 168. Thegenerator 230 stores various information obtained throughout the sizingprocess, such as the estimated diameter of the esophagus, thecalibration balloon volume, the number of sizing performed and themeasured diameters.

FIG. 17 illustrates a schematic of an exemplary mechanism for performingballoon sizing using a mass flow meter and pressure sensors. Using thismechanism, the generator 230 monitors and controls the pressure in theballoon and estimates the volume within the balloon. Pump 171 suppliescompressed air to the solenoid valve 172, which can switch the flow ofair for either inflating or deflating the balloon. Prior to the gasentering the pump 171, filter 170 removes particulates from the gas thatwill enter the pump 171. The mass flow sensor 173 senses the mass of aircoming in the system. In addition, the flow sensor 173 could be used tomeasure the flow of air out of the system for enhanced safety andaccuracy of the system. The pressure within the system is measured bypressure sensors 174 and 175, with sensor 175 measuring the atmosphericpressure. Alternatively, instead of sensing the pressure within thesystem, a positive displacement pump may be used to pump a known amountof fluid or gas into the balloon. When the balloon is deflated, the airflows from the inside of the balloon to the mass flow sensor 173.Filters 176 and 179, connected by python cable 178, preventcontamination of the mass flow sensor 173 and pump 171 during deflation.

It should be noted that the sizing method and system described hereinmay be used for estimating the inner diameter or other cross-sectionalparameters of any body lumens or passageways, for example for lumenswithin the gastrointestinal tract, vasculature, urinary tract,urogenital system or pulmonary system.

Once the size of the esophagus is estimated for a set pressure, anappropriate treatment catheter is connected to the generator in order toablate abnormal cells within the esophagus. The diameter of the balloonof the attached treatment catheter is read from the storage device. Itshould be noted that, in an alternate embodiment, treatment of theesophagus may be performed using the same catheter and balloon used forsizing. In such embodiment, the generator would recognize the catheter'sdual function, sizing/treatment, and would read the appropriateparameters from the storage device.

Referring to FIG. 21, after the ablation balloon diameter is read fromthe storage device, the diameter is displayed on display 250. Based onthe recommended size of the treatment catheter, the appropriategenerator settings are retrieved from the storage device, such as:balloon inflation pressure, balloon volume data, default, maximum orminimum power settings, default, maximum or minimum energy settings, orsize of the electrodes. Thus, the energy density and power levels can beautomatically set according to the size of the treatment catheter. Thepreset power level is displayed on display 244, while the preset energydensity level is displayed on display 248.

The generator 230 then inflates the balloon of the attached treatmentcatheter to a preset pressure of approximately 7 psig, which will bedisplayed on display 251. The set indicator 254 indicates the unit is instand-by mode, when all the values are being set. In the standby mode,all the set values are displayed. Throughout the entire ablationprocedure, it is desirable to maintain the pressure on the balloon at asteady pressure as a safety precaution. If the balloon stays at apressure of at least 6.5 psig (typical pressure values range from0.5-200 psig), the system is then considered “armed.” The arm indicator256 indicates that the displayed values are the set values and thesystem is ready to deliver RF energy. The RF on/off switch 238 indicatesand controls when RF power is being delivered. In one embodiment, thegenerator 230 delivers and controls power until the desired energydensity is delivered. The generator maintains a set power on eachelectrode and is capable of sequentially delivering energy to eachelectrode on the treatment catheter. When the desired energy isdelivered to all the desired locations, the completed indicator 258indicates the ablation is completed.

A user may have the capability to adjust the power and the energydensity delivered to the tissue. The output power can be set andadjusted using the up and down buttons 241. The actual power deliveredto the tissue from the catheter leads is displayed on the power display244. Similarly, the energy density is set using the up and down button246 and the output energy density delivered is displayed on the LEDdisplay 248.

The system status display 252 is an LCD panel and displays operationalcodes and user instructions. For example, the panel 252 displays the“Calibration” function prior to performing auto-sizing of the balloon.The panel 252 also displays error codes and an error message withinstructions for solving errors. The reset button 262 may be pressed toreset the system if an error occurs. Further, the panel 252 indicateswhen the system is in standby mode. The fault indicator 260 indicateswhen the system is in the fault mode and a non-recoverable error wasdetected. It should be noted that the front panel of the generator 230may display, control and indicate functions other than the exemplaryfunctions described herein.

In one embodiment, pedal-type footswitch 232 is attached to thegenerator rear panel and may control the inflation system and RFdelivery. The pedal 232 is capable of duplicating certain functions ofthe generator front panel buttons. For example the footswitch 232 mayduplicate the RF on/off button 238 and/or the balloon auto inflation upand down buttons 240 and 241.

FIG. 18 is an exemplary flowchart of the ablation procedure according toone embodiment of the invention. When the ablation catheter is connectedto the generator, at step 180, the generator recognizes the specificcharacteristics of the ablation catheter and is ready to inflate theballoon, at step 181. The catheter is armed at 182 and the balloon isinflated and maintained at a pressure of approximately 7 psig (typicalpressure values range from 0.5 to 200 psig). If the balloon pressure issteady, the ARM indicator is lit on the front panel display of thegenerator. At step 183, once the ARM light is on, the generator is readyfor delivering energy to the electrodes of the ablation catheter. Theenergy is subsequently automatically delivered by the generator 230, asshown at step 184. After each ablation, the balloon is automaticallydeflated in order to reposition the balloon and the electrodes toanother ablation location within the esophagus. A series of subsequentablations are performed as needed at step 186. After treating all thedesired locations within the esophagus, the ablation is complete at step188.

It should be noted that the generator delivers energy only after thesystem meets certain safety checks, as shown at steps 185 and 187. Thegenerator periodically monitors balloon inflation, energy parameters andoverall system integrity before and during the tissue treatment. Thesesafety procedures ensure that the generator can safely deliver therequired power. For example, the generator will not deliver power to theelectrodes unless the impedance and temperature of the tissue are withinacceptable parameters. Similarly, the generator monitors any pressurefluctuations within the treatment balloon. In one embodiment, thegenerator 230 will only deliver power if the balloon inside theesophagus is maintained at a steady required pressure of approximately7+/−1 psig. This safety check ensures that there is no connection leakor balloon leak and the esophagus is fully distended prior to ablation.Another precaution is taken with respect to deflation of the balloonbetween ablations. In order to ensure that the balloon is fully deflatedbefore repositioning it to a different location within the esophagus,the balloon is deflated to a pressure of approximately −2 psig.

In one embodiment, the generator 230 monitors and controls the poweroutput to the electrodes and ensures that a constant power is delivered.A proportional integral derivative (PID) controller controls the amountof power by increasing the power level, and inherently the voltagelevel, until it reaches a set target valued. In one embodiment, the PIDcontroller controls the amount of power by gradually increasing thepower level. In a particularly advantageous embodiment, the PIDcontroller controls the amount of power by rapidly increasing the powerlevel. Further, to better control the ablation depth, the PID controllermakes sure that the desired power level is achieved within a certaintime window. In one embodiment, the generator is adapted to control theamount of energy delivered to the tissue over time based on the measureddiameter of the esophagus. Furthermore, the generator can be adapted tonormalize the density of energy delivered to the tissue over time basedon the measured diameter of the esophagus so that equivalent energydensities (i.e., energy per unit are of electrode surface area {J/cm²})are delivered to esophagi of differing diameters. In another embodiment,the generator is adapted to control the amount of power delivered to thetissue over time based on the measured diameter of the esophagus so thatequivalent power densities (i.e., power per unit area of electrodesurface area {W/cm²}) are delivered to esophagi of differing diameters.

In order to effectively ablate the mucosal lining of the esophagus, thesystem described herein controls the total energy delivered to theesophageal tissue and the amount of time for which the energy isdelivered, as described above. Other methods may be similarly employedto ablate a desired surface area rapidly and circumferentially, whilecontrolling the ablation depth. The generator 230 may be manuallycontrolled by a user such that the amount of power density delivered tothe esophageal tissue can be monitored over time. As such, the generator230 is adapted to allow the user to select an appropriate power densityto be delivered to the tissue in short burst. In one embodiment, thetime for an effective treatment is less than one second. In anotherembodiment, the time is approximately 300 ms.

In order to effectively eliminate abnormal cells in the esophagus,energy must be applied such that a physiological change occurs at thecellular level within the esophagus lining. Methods of tracking thecharacteristics of the esophageal tissue and the changes in its cellularcharacteristics include monitoring the tissue impedance and/or thetissue temperature. The ablation time could be then adjusted based onthe individual characteristics of the tissue and its measured impedanceand/or temperature values.

FIG. 19 illustrates a graphical representation of impedance measurementsduring ablation over time. During ablation, the tissue temperaturerises, which causes a decrease in the tissue resistivity. This drop inimpedance from an initial impedance value is represented by theexemplary reference points A and B. If the ablation continues beyond thereference point B, the tissue cell membranes rupture such thatdesiccation of cells occurs and resistivity of the tissue increases. Theexemplary increased impedance value measured during this period of timeis shown by reference point C. In order to control the depth of ablationand the extent of treatment in terms of the total volume of tissuedesiccated, the generator 230 monitors the changes in the measuredtissue impedance values. As such, the generator 230 delivers the energyto the tissue in a time window defined by the tissue impedancemeasurements. For example, in one embodiment, generator 230 may ablateonly for the time it takes the tissue to reach an absolute impedancetarget. For example, the target targeted impedance value ranges fromapproximately 0.5-10 ohms. In another embodiment, generator 230 mayablate only until the impedance value decreases a pre-determinedpercentage from the initial impedance value of the tissue prior toablation. Yet, in another embodiment, the time of ablation can depend onthe point at which the impedance values reach an inflection point on thegraph illustrated in FIG. 19, i.e., when the impedance values arebetween the reference points B and C. As such, the energy delivery couldcease when the impedance reaches its minimum value, at which point itstarts to increase. In another embodiment, the ablation time may bedefined by the impedance value that exceeds a particular level. If thetissue impedance value reaches levels higher then the initial impedancevalue, as shown by the exemplary reference point D, the extent of thetreatment may reach levels such that the esophageal wall is breached. Assuch, it may desirable to cease delivering energy to the tissue beforethe impedance reaches its initial value, e.g., reference value C.

FIG. 20 illustrates a graphical representation of the tissue temperatureover time. When the tissue receives RF energy, heat is being generated.T1, T2 and T3 represent temperature curves of different sensorspositioned at different locations within or outside the tissue to beablated. For optimal ablation with controlled depth, the ablation timeshould be controlled such that the temperature of the tissue is lessthan 100° C. For example, if the desired ablation reaches inside thetissue approximately ½ to 1 millimeter from the surface, the generator230 controls the ablation time such that the temperature of the tissueis between 65° C. and 95° C. Alternatively, the ablation time could bedefined by the amount of time that it takes the tissue to heat to apreset target temperature. In this method, the generator 230 monitorsthe temperature of the tissue and, when the tissue has reached a certaintemperature, generator 230 stops the delivery of the energy to thetissue.

While the exemplary embodiments have been described in some detail, byway of example and for clarity of understanding, those of skill in theart will recognize that a variety of modification, adaptations, andchanges may be employed. Hence, the scope of the present inventionshould be limited solely by the appending claims.

The invention claimed is:
 1. An apparatus for treating an esophagus,comprising: a generator having a source of RF energy connected to agenerator electrical connector and a pump connected to a generatorpneumatic connector; and a sizing and treatment catheter having aproximal end and a distal end, an electrical connector configured forattachment to the generator electrical connector and a pneumaticconnector on the proximal end configured for attachment to the generatorpneumatic connector and a balloon on the distal end of the catheter incommunication with the pneumatic connector and an electrode array on anexterior surface of the balloon in communication with the electricalconnector; wherein, when the sizing and treatment catheter is connectedto the generator electrical connector and the generator pneumaticconnector, the generator is configured to: (i) measure an internalpressure of the balloon; (ii) inflate the balloon with an expansionmedium until the internal pressure is equal to a predetermined targetpressure; (iii) measure the expansion medium delivered to the balloonwith a mass-flow meter until the predetermined target pressure isreached; (iv) determine a dimension of the esophagus based on the amountof expansion medium in the balloon at the predetermined target pressure;and (v) deliver energy to the electrode array.
 2. The apparatus of claim1, wherein the generator is further configured to deflate the balloonafter delivery of energy to the electrode array.
 3. The apparatus ofclaim 1, wherein the predetermined target pressure is between about 1psig and about 10 psig.
 4. The apparatus of claim 1, wherein thepredetermined target pressure is between about 4 psig and about 7 psig.5. The apparatus of claim 1, wherein the predetermined target pressureis between about 2 and about 3 psig.
 6. The apparatus of claim 1,wherein the predetermined target pressure is sufficient to inflate theballoon to engage with and unfold the walls of the esophagus.
 7. Theapparatus of claim 1, wherein the generator is configured to deliversufficient energy to the electrode array to accomplish ablation ofmucosal or submucosal level esophageal tissue.
 8. The apparatus of claim1, wherein the generator is configured to deliver sufficient energy tothe electrode array to sear the lining of the esophagus based on thedetermined dimension of the esophagus.
 9. The apparatus of claim 1,wherein the generator is configured to deliver sufficient energy to theelectrode array to sear the lining of the esophagus in less than 5seconds.
 10. The apparatus of claim 1, wherein the generator isconfigured to normalize the density of energy delivered to the electrodearray over time based on the determined dimension of the esophagus. 11.The apparatus of claim 1, wherein the generator is configured to deliversufficient energy to the electrode array to deliver an energy densityfrom 1 J/cm2 to 50 J/cm2 to sear the lining of the esophagus.
 12. Theapparatus of claim 1, wherein the generator is configured to deliversufficient energy to the electrode array to sear the lining of theesophagus by delivering energy to different circumferential sections ofthe esophageal wall sequentially in less than 5 seconds.
 13. Theapparatus of claim 1, wherein the balloon has a native diameter that islarger than an expected diameter of the esophagus.
 14. The apparatus ofclaim 1, wherein the electrode array is positioned on an electrodesupport comprising a flexible, non-distensible backing.
 15. Theapparatus of claim 14, wherein the electrode support is furled around acircumference of the balloon.
 16. The apparatus of claim 15, wherein theelectrode support at least partially overlaps itself.
 17. The apparatusof claim 15, wherein the electrode support is configured to unfurl asthe balloon is inflated.
 18. The apparatus of claim 17, furthercomprising an elastic member coupled with the electrode supportconfigured to retain the electrode support in contact with the balloon.